Project description
Designing proteins that bind to nucleic acids
Proteins that bind nucleic acids such as DNA or RNA control cellular processes, and their malfunction can cause diseases such as cancer and autoimmunity. Unfortunately, these interactions are hard to target with conventional drugs because their contact surfaces are large and complex. The ERC-funded NAMPify project aims to create a new class of protein-based tools that imitate nucleic acids and can precisely regulate nucleic acid-binding proteins. Researchers will develop advanced computational methods for the design of such proteins, taking into consideration the structure and chemistry of nucleic acids. These methods will also provide insight into the structure of protein-nucleic acid complexes, with potential applications in medicine.
Objective
Protein–nucleic acid (NA) interactions are fundamental to many cellular processes, and their disruption can lead to diseases such as autoimmune disorders and cancer. However, targeting NA-binding proteins with small molecules is difficult due to the “undruggable” nature of their interfaces. Recent advancements in computational protein design and deep learning have created new opportunities for the development of protein-based therapeutics. However, current methods struggle to design proteins that can effectively modulate or mimic the intricate protein-NA interactions directly. While some NA-aware models have been developed, they often underperform due to our limited understanding of protein-NA interactions and the scarcity of diverse structural training data. To overcome these challenges, I propose to pioneer the design of NA-mimicking proteins (NAMPs) capable of directly modulating protein-NA interactions with high specificity and adaptable functionality. I will develop computational methods that incorporate the structural and chemical features of NAs, and create NAMPs tailored to engage therapeutically relevant NA-binding proteins and regulate their activity. In addition, I will develop approaches to expand the structural data on protein-NA complexes using accelerated structure determination methods to refine NA-aware models. This will enable the design of NA-binding proteins with sequence- and shape-specific recognition. Lastly, to create molecular machines with complex functionalities, I will develop new methodologies for the de novo design of multi-domain proteins capable of adopting multiple, defined conformations—long considered a “holy grail” in protein design. By integrating these approaches, I aim to overcome the current limitations in studying and designing protein-NA interactions, paving the way for the creation of sophisticated molecular tools with vast applications in synthetic biology, biotechnology, and medicine.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
You need to log in or register to use this function
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-STG
See all projects funded under this callHost institution
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
8006 Zurich
Switzerland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.